Most head and neck cancer (HNC) patients receive radiotherapy (RT) as part of their cancer management. Radiation exposure results in permanent damage to the salivary glands, causing loss of function and subsequent RT-related xerostomia or dry mouth. Patients with RT xerostomia experience reduced quality and quantity of saliva, which leads to considerable morbidities, including solid food dysphagia, chronic dental caries, recurrent oral infections and rare mandibular osteoradionecrosis. It is estimated that >80% of patients receiving head and neck RT suffer from many of these side effects. Current approved medical managements for RT xerosomia include the use of salivary substitutes, lubricants and cholinergic agonists to stimulate salivary secretion. These treatments remain palliative in nature, require chronic use and are often ineffective. Intensity modulated radiotherapy (IMRT) can protect the parotid glands from direct radiation injury in selective cases; however, it often cannot spare the submandibular glands (SMG), which are responsible for resting saliva production. The vicinity of the SMG to the level II nodes, which are the most commonly involved nodes in HNC, makes it harder to spare them from direct RT beams. At least one randomized study indicated that although IMRT resulted in improved parotid sparing and more stimulatory saliva production, it did not result in significant improvement of patient's subjective xerostomia. In contrast, SMG transfer and sparing from direct RT beams was associated with a significantly better subjective xerostomia function as assessed by xerostomia and quality of life questionnaires. Therefore, despite widespread IMRT use in HNC, development of methods to reconstitute salivary gland tissue, specifically SMG, and recovery of physiological salivary secretion after RT is needed in HNC patients.